Summary of Work: DFNB3 is a mutant allele of a presently unidentified gene that causes recessive nonsyndromic profound congenital hearing impairment. DFNB3 was mapped to the pericentromeric region of chromosome 17 ( Friedman et al. 1993, Nature Genetics). The goal of this project is to clone DFNB3 and understand its essential biological function in the auditory system. To this end we have: (1) identified families from India with congenital recessive hearing impairment due to mutations in DFNB3, (2) refined the map position of DFNB3 to 17p11.2 and are now examining candidate genes in this region for mutations. The shaker-2 mutation in the mouse is on chromosome 11 and is likely to be the murine homologue of DFNB3. In collaboration with scientists at the University of Michigan we are cloning the gene that causes shaker-2.